Kenneth M. Dürsteler

Rapid cortical hemoglobin deoxygenation after heroin and methadone injection in humans: a preliminary report.

The short-term effects of intravenous opioids (heroin 20-300 mg, methadone 30-180 mg) on cortical hemoglobin oxygenation were examined by near infrared spectroscopy in ten opioid-dependent subjects and were compared with the effects of saline in ten age-matched normal controls. Heroin and methadone produced a rapid and dramatic decrease in cortical hemoglobin oxygenation. Saline had no effects. Opioid-induced acute deoxygenation of cortical hemoglobin is most likely associated with respiratory depression. Thorough medical monitoring is strongly recommended in intravenous opioid maintenance treatments.

Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

Background Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder. Conclusion Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by specific study characteristics, among them dosing, duration of treatment, or sample size. This needs to be considered when discussing the potential of MPH as replacement therapy for cocaine dependence. Finally, based on the results, we suggest possible directions for future research.

A comprehensive model of treatment participation in chronic disease allowed prediction of opioid substitution treatment participation in Zurich, 1992-2012

OBJECTIVES Chronic diseases are often associated with cycling in and out of treatment. We used data of a large opioid substitution treatment case register to (1) identify associated factors and (2) integrate retention and readmission into a model of overall participation over subsequent treatment episodes of various groups. STUDY DESIGN AND SETTING Data of all 9,407 patients undergoing 26,545 methadone or buprenorphine substitution treatment episodes between 1992 and 2012 in the canton of Zurich, Switzerland, were analyzed. We used extended survival analysis to estimate the duration of, and time between, treatment episodes, with the number of episodes, gender, nationality, administration route, age at onset of first regular heroin use, and provider type as independent variables. A similar analysis was applied to estimate overall participation (the probability of being in treatment at a given day after first entry independent of current number of treatment episode) and to test for group differences. RESULTS The time between treatment episodes shortened with the increasing number of episodes. Retention slightly increased after the first episode and then shortened for later treatment episodes. Effect sizes were generally rather weak (odds ratio ≤ 1.47). Effects were usually equal for all episodes, and if changing, weakened for later episodes. CONCLUSION The complex process of leaving and entering treatment as well as the daily probability of being in treatment independent of treatment episode can be predicted by comprehensible statistical models applied to patient-period data sets.

Similar and Different? Subjective Effects of Methylphenidate and Cocaine in Opioid-Maintained Patients

ABSTRACT Methylphenidate (MPH) is commonly prescribed for attention deficit hyperactivity disorder (ADHD). Recreational nonmedical use has been described and also occurs in patients on opioid maintenance treatment (OMT). MPH has been proposed for use as replacement therapy in cocaine dependence, although evidence for efficacy is inconclusive. We conducted a cross-sectional interview study on patterns of MPH use in a sample of 20 MPH-using patients on OMT with a history of cocaine use. We assessed symptoms of depression, ADHD during childhood, and retrospective subjective-effects profiles of MPH and cocaine. Risky patterns of MPH use were common, in particular illicit acquisition, use of high doses, and parenteral administration. Sixty percent of patients reported having used MPH as a substitute for cocaine. Correspondingly, the subjective-effect profiles of MPH and cocaine showed striking parallels, with overall effects of MPH being rated more positively than those of cocaine. Proportions of patients with elevated scores for depression or childhood ADHD were large, highlighting the importance of treating dual disorders in this population. Clinical studies on MPH substitution in cocaine-dependent patients on opioid maintenance treatment could benefit from consideration of the patterns of application of MPH in this population. Results are preliminary due to small sample size.

Effect of Door-Locking Policy on Inpatient Treatment of Substance Use and Dual Disorders

Objective: Substance use treatment is often performed inside locked wards. We investigate the effects of adopting a policy of open-door treatment for a substance use treatment and dual diagnosis ward. Methods: This is a prospective open-label study investigating 3-month study periods before opening (P1), immediately after (P2), and 1 year after the first period (P3). Data on committed patients, coercion (seclusion, forced medication, absconding events with subsequent police search), violence, and substance use was collected daily. We applied generalised estimating equation models. Results: The mean daily number of patients with ongoing commitment changed from 2.64 (P1) to 2.12 (P2) to 0.96 (P3), corresponding to a reduction of relative risk (RR) for having an ongoing commitment by 20% in P2 (RR 0.80; 95% CI 0.66-0.98) and 67% in P3 (RR 0.33; 95% CI 0.25-0.42). The mean daily number of coercive events was 0.29, 0.13, and 0.05, corresponding to a risk for undergoing coercive measures reduced by 56% (RR 0.44; 95% CI 0.22-0.90) and 85% (RR 0.15; 95% CI 0.05-0.45). Substance use, violence or ward atmosphere did not differ significantly. Conclusions: Our results support findings from general psychiatric wards of reduced coercion after adopting a primarily open-door policy. However, coercive events were rare during all periods. The widespread practice of restricting the freedom of inpatients with substance use disorders by locking ward doors is highly questionable.

Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the “Bernese method”

Background Buprenorphine is a partial µ-opioid receptor agonist used for maintenance treatment of opioid dependence. Because of the partial agonism and high receptor affinity, it may precipitate withdrawal symptoms during induction in persons on full µ-opioid receptor agonists. Therefore, current guidelines and drug labels recommend leaving a sufficient time period since the last full agonist use, waiting for clear and objective withdrawal symptoms, and reducing pre-existing full agonist therapies before administering buprenorphine. However, even with these precautions, for many patients the induction of buprenorphine is a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the full agonist bears the risk of relapse to illicit opioid use. Cases We present two cases of successful initiation of buprenorphine treatment with the Bernese method, ie, gradual induction overlapping with full agonist use. The first patient began buprenorphine with overlapping street heroin use after repeatedly experiencing relapse, withdrawal, and trauma reactivation symptoms during conventional induction. The second patient was maintained on high doses of diacetylmorphine (ie, pharmaceutical heroin) and methadone during induction. Both patients tolerated the induction procedure well and reported only mild withdrawal symptoms. Discussion Overlapping induction of buprenorphine maintenance treatment with full µ-opioid receptor agonist use is feasible and may be associated with better tolerability and acceptability in some patients compared to the conventional method of induction.

Changes in substance use in patients receiving opioid substitution therapy and resulting clinical challenges: a 17-year treatment case register analysis

BACKGROUND Although the beneficial effects of opioid substitution for the reduction of heroin use are well established, its effect on other substance use is unclear. We aimed to evaluate short-term and long-term changes in substance use in opioid-dependent patients on opioid substitution therapy. We focused on frequent use of heroin, cocaine, benzodiazepines, and alcohol under naturalistic conditions (ie, with non-selected patients and clinical practice as usual) over 17 years. METHODS This was a treatment case register analysis. Data were obtained from the treatment case register of the canton of Zurich, Switzerland, which included information for 8962 patients (122 399 case report forms) who received substitution therapy with methadone or buprenorphine between 1998 and 2014. The main focus of our study was to evaluate long-term changes in frequent substance use of patients on opioid substitution therapy, together with the associations between individual, treatment, and environmental factors and substance use, including short-term changes at first treatment entry. Data were analysed using a generalised estimating equation that accounted for individual, treatment, and environmental factors. Frequent use was defined as substance use on at least 5 days per week. FINDINGS The most frequent use of heroin (odds ratio [OR] 5·30, 95% CI 4·63-6·08; p<0·0001), cocaine (2·30, 1·95-2·71; p<0·0001) and, to a lesser extent, benzodiazepines (1·34, 1·17-1·54; p<0·0001) and alcohol (1·21, 1·08-1·35; p=0·0007), was found in previously untreated individuals compared with patients already receiving treatment 6 months after starting opioid substitution therapy, corroborating a strong effect of initiating substitution therapy. Frequency of substance use was associated with the year of evaluation: frequent use of heroin (OR per decade 0·56, 0·52-0·60; p<0·0001) and cocaine (0·63, 0·58-0·68; p<0·0001) significantly decreased between 1998 and 2014, while frequent alcohol use increased (1·15, 1·08-1·23; p<0·0001). In 2014, frequent alcohol use was observed in 990 (22·5%) of 4400 patients on opioid substitution therapy. INTERPRETATION Frequent use of alcohol during opioid substitution therapy significantly increased during the observation period, whereas there was a decline in frequent use of heroin and cocaine. Given the high infection rates with hepatotoxic viruses and the increasing liver-related mortality rates in patients on opioid substitution therapy, these findings suggest that frequent alcohol use increasingly constitutes a therapeutic challenge in opioid substitution therapy. FUNDING None.

Psychosis After Switch in Opioid Maintenance Agonist and Risperidone-Induced Pisa Syndrome: Two Critical Incidents in Dual Diagnosis Treatment

ABSTRACT Background and aims: Dual diagnosis commonly occurs among patients with an opioid use disorder. Treatment is ideally performed in an integrated fashion. We present a case that illustrates the complex and challenging psychiatric and medical therapy of such patients in the light of the literature. Case description: We report on a 56-year-old patient with schizophrenia and opioid dependence who experienced both risperidone-induced Pisa syndrome and, 3 years later, acute psychosis after switching the opioid substitution medication from methadone to slow-release oral morphine due to QT prolongation. Conclusions: With the current availability of a diversity of substitution opioids in Switzerland (methadone, buprenorphine, diacetylmorphine, sustained-release oral morphine), studies on differential effectiveness of these agents in opioid-dependent subpopulations with selective comorbidity profiles are desirable. The same is true for further investigation of the involvement of the opioid receptor system in schizophrenia. In clinical practice, any alteration of opioid medication in patients with dual diagnosis and a history of schizophrenia should be accompanied by close observation for psychotic symptoms.

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting

Background: Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. Methods: All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Results: Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient’s therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Conclusions: Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient’s empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare professionals.

Novel Medication Supply Model Guarantees Adequate Management and High Adherence to Polypharmacy in Older Opioid Users – Preliminary Results with Outpatients

Background: Life expectancy of older drug users has increased, primarily thanks to opioid agonist treatment (OAT). Nursing homes are often not adapted to accommodate patients with substance use disorders. Although care and adherence to polypharmacy in older opioid users need considerable resources e.g., daily visits to an outpatient clinic, outpatient treatment and surveillance are provided as long as possible. We developed a novel medication supply model with an electronic dispenser of pre-packed medications located at patient home, after allowing for law requirements concerning the dispensing of opioids, and present preliminary results from three illustrative outpatients. Methods: The community pharmacy provided unit-of-dose pouches with all solid oral medications directly to patient home. Opioids for substitution were obtained at the addiction clinic in at least weekly intervals, otherwise in the pouches. The pouches were loaded into a lockable, remote-controlled medication management aid that was programmed according to the patient’s medication schedule. The dispenser reminds patients with acoustic alerts to take their medication and records dates and times of medication retrievals. It automatically sends an alert if a patient misses to retrieve a dose. Results: Our three outpatients used the electronic dispenser during 659, 118 and 61 days, with a total of 5, 9, and 18 pills to take daily at 1, 3 and 5 intake times, respectively. The majority of the doses were taken on the preset time (94%, 68.2% and 73.7%) or deliberately in advance (pocket dose). Clinical benefits were initiation and maintenance of a therapy for dementia over 18 months and suppression of HIV viral load over 1.8 years (patient 1), prevention of further dose escalation of pain medication (patient 2) and release of prompts to initiate the existential task of cooking (patient 3). Conclusion: Our novel supply model allows adequate implementation and persistence of complex treatments with outpatients. Clinical outcomes improved, patients and caregivers were satisfied, and resources were saved.